M ET ABOL I SM CL IN I CA L A N D E XP E RI ME N TAL 6 4 ( 2 0 15 ) 33 83 47

Available online at www.sciencedirect.com

Metabolism
www.metabolismjournal.com

Effect of lifestyle intervention in patients with type 2

diabetes: A meta-analysis
Liang Chen, Jian-Hao Pei, Jian Kuang, Hong-Mei Chen, Zhong Chen,
Zhong-Wen Li, Hua-Zhang Yang
The First Division in Department of Endocrinology, Guangdong General Hospital, Guangdong Academy of Medical Sciences,
106th of Zhongshan Er Road, Guangzhou 510080, China

A R T I C LE I N FO
Article history:

AB S T R A C T
Objective. The effect of lifestyle intervention on clinical risk factors in patients with type

Received 16 June 2014

2 diabetes is unclear. The aim of this meta-analysis was to evaluate the effects of

Accepted 19 October 2014

comprehensive lifestyle change, such as diet, exercise, and education, on clinical markers
that are risk-factors for cardiovascular disease in patients with type 2 diabetes.

Keywords:

Methods. We searched Medline, Cochrane, EMBASE, and Google Scholar (up to August 31,

Lifestyle

2013) for randomized controlled trials that compared standard of care (control group) with

Intervention

treatment regimens that included changes in lifestyle (intervention group). The primary

Type 2 diabetes

outcome was reduction in risk factors of cardiovascular disease including body mass index

Meta-analysis

(BMI), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP),
high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c).
Results. A total of 16 studies were included in the meta-analysis. The standardized difference
in means of change from baseline significantly favored the intervention compared with the
control group in BMI (0.29; 95% CI, 0.52 to 0.06, P = 0.014), HbA1c (0.37; 95% CI, 0.59 to 0.14,
P = 0.001), SBP (0.16: 95% CI, 0.29 to 0.03, P = 0.016), DBP (0.27, 95% CI = 0.41 to 0.12,
P < 0.001). There was no difference between the intervention and control groups in HDL-c (0.05;
95% CI, 0.10 to 0.21; P = 0.503) and LDL-c (0.14; 95% CI, 0.29 to 0.02; P = 0.092).
Conclusions. The meta-analysis found that lifestyle intervention showed significant
benefit in risk factors that are known to be associated with development of cardiovascular
disease in patients with type 2 diabetes.
2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NCND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

1.

Introduction

The proportion of people with type 2 diabetes is on the rise

and is a major cause of death world-wide. Type 2 diabetes is a
major risk factor for vascular disease with 65% of all diabetic
deaths being due to cardiovascular disease [1].
Lifestyle characteristics, such as physical activity, diet, and
stress are important factors that influence development and

prognosis of type 2 diabetes [2]. Changes in diet and increase

in physical activity (walking, etc.) and exercise (running,
cycling, etc.) are key components of the management of type
2 diabetes [3], and guidelines recommend changes in these
lifestyle characteristics for both prevention and management
of the disease [4].
Several systematic reviews and meta-analyses have reported the benefit of interventions aimed at improving lifestyle

Abbreviations: BMI, body mass index; HbA1c, glycated hemoglobin; SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL-c,
high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol.
Corresponding author. Tel.: +86 13538785491.
E-mail address: acchenliang@gmail.com (L. Chen).
http://dx.doi.org/10.1016/j.metabol.2014.10.018
0026-0495/ 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.
org/licenses/by-nc-nd/3.0/).

M ET ABOL I SM CL IN I CA L A N D EX PE RI ME N TA L 6 4 ( 2 0 15 ) 33 83 4 7

behaviors on disease progression and development of comorbidities (eg, vascular disease) in patients with type 2
diabetes [513]. However, the benefit of lifestyle changes in
reducing all-cause mortality or cardiovascular disease is less
clear as the findings from these analyses are inconsistent or the
data are inconclusive [513]. To our knowledge, there have been
no meta-analyses that evaluated the effect of interventions that
result in multiple lifestyle changes on risk factors for cardiovascular disease in patients with type 2 diabetes. The aim of this
meta-analysis was to evaluate the effects of changes in lifestyle
that included dietary behavior, exercise, or physical activities on
clinical markers of cardiovascular disease in patients with type
2 diabetes.

2.

Materials and methods

2.1.

Search strategy

We searched Medline, Cochrane, EMBASE, and Google Scholar

for randomized controlled trials that compared standard care
with interventions that involved changes in lifestyle. The
following terms were used in the search: diabetes, cardiovascular risk, lifestyle, health education, dietary, exercise/physical
activities, and behavioral intervention. Articles up to August 31,
2013 were included. Studies were excluded if they were not
published in English, were not prospective randomized trials,
did not enroll patients with type 2 diabetes, or did not
investigate lifestyle or education programs relating to dietary
behavior, exercise, or physical activities. All possibly relevant
studies were also hand-searched by 2 independent reviewers
and both reviewers had to agree for the study to be included. If
there was disagreement, it was resolved by a third reviewer.

2.2.

Data extraction

The following information or data were extracted from the

included studies: the name of the first author, year of publication, study design, number of participants in each treatment
group, participants' age and gender, diagnostic criteria, intervention regiment for study/control group, and results.

2.3.

Quality assessment

The included studies were assessed for risk bias using the Risk
of Bias assessment tool, Review Manager 5.1, and recommendations for judging risk of bias provided in Chapter 8 of the
Cochrane Handbook for Systematic Reviews Interventions [14].

2.4.

339

the percentage of the total variability in effect estimates

among trials resulting from heterogeneity rather than chance.
Random-effects models of analysis were used if heterogeneity
was detected (I2 > 50%). Otherwise, fixed-effects models were
used. For each risk factor measure, standardized difference in
means with corresponding 95% confidence intervals (CIs) was
calculated for between groups and among studies. A twosided P value < 0.05 indicated statistical significance for one
comparison group over the other. Sensitivity analysis was
carried out for the risk factors BMI and HbA1c using the leave
one-out approach. A funnel plot, the fail-safe N (which
indicates whether the observed significance is spurious or
not), and Egger's test (which detects whether the observed
studies is asymmetric or not) were used to assess possible
publication bias. All analyses were performed using Comprehensive Meta-Analysis statistical software, version 2.0 (Biostat,
Englewood, NJ).

3.

Results

3.1.

Characteristics of included studies

Eighty-five possible studies were identified and 18 were excluded

owing to not being relevant to this analysis (Fig. 1). Of the 67
remaining studies, 51 were excluded due to being redundant
with an included study, not presenting outcomes of interest,
having an intervention period of <6 months, not using behavior
or exercise programs, only having one gender in the study, or
having >2 treatment arms. One study [15] met the inclusion
criteria but was excluded because its findings, in regard to BMI,
LDL-c and HDL-c changes, were not in concordance with the
included studies. The inclusion of this study would have skewed
the meta-analysis by increasing the discrepancy in both
sensitivity and publication bias analyses (Fig. 1). A total of 16
studies were included in the meta-analysis [1631].
The number of patients per study ranged from 23 to 2575
(Table 1). The mean (SD) age was similar across studies
(range, 51.3 [1.8] to 67.3 [19]) and between the interventional and
control groups (Table 1). The proportion of patients that were
male ranged from 34.8% to 98%, and the lengths of the study
ranged from 6 months to 8 years (Table 1). Supplementary
Table S1 summarizes the change from baseline of key risk
factors for all included studies.
Quality assessment indicated that all 16 studies had a high
risk of performance bias due to the studies not having
adequate blinding of the participants and personnel (Fig. 2A
and B). Six studies had high risk of bias due to risk factor
assessments not being blinded (Fig. 2B) [16,2224,30,31].

Statistical analysis
3.2.

The primary outcome was reduction in any risk factor of

cardiovascular disease including body mass index (BMI),
HbA1c, systolic blood pressure (SBP), diastolic blood pressure
(DBP), high-density lipoprotein-c (HDL-c), and low-density
lipoprotein-c (LDL-c). BMI, HbA1c, SBP, DBP, HDL-c, and LDL-c
were compared between participants having intensive lifestyle intervention (intervention group) and conventional
intervention (control group). A 2 based test of homogeneity
was performed using Cochran's Q statistic and I2. I2 illustrates

Body mass index

Eleven of the included studies reported change from baseline

in BMI [1820,2225,27,28,30,31]. There was heterogeneity
for BMI across studies (Q statistic = 71.93, I 2 = 86.10%,
P < 0.001); hence, a random effects analysis was applied. The
standardized difference in means of change from baseline
in BMI significantly favored the intervention group over the
control group (standardized difference in means, 0.29; 95%
CI, 0.52 to 0.06, P = 0.014) (Fig. 3).

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M ET ABOL I SM CL IN I CA L A N D E XP E RI ME N TAL 6 4 ( 2 0 15 ) 33 83 47

Fig. 1 Flow chart for study selection.

3.3.

HbA1c

All 16 studies reported data for change from baseline in

HbA1c. A random effects analysis was applied owing to
evidence of heterogeneity among the studies (Q statistic =
238.84, I2 = 93.72%, P < 0.001). The standardized difference in
means of change from baseline in HbA1c significantly favored
the intervention group compared with the control group
(standardized difference in means, 0.37; 95% CI, 0.59 to
0.14, P = 0.001) (Fig. 3).

3.4.

Systolic and diastolic blood pressure

Fifteen of the 16 studies reported values for SBP at baseline

and following intervention [1628,30,31] and 14 reported DBP
[1625,27,28,30,31]. There was heterogeneity across the studies in both SBP and DBP (SBP: Q statistic = 64.03, I2 = 78.13%,
P < 0.001; DBP: Q statistic = 73.51, I 2 = 82.32%, P < 0.001);
consequently, a random effects analysis was used. The
standardized difference in means of change from baseline in
both SBP and DBP significantly favored the intervention (SBP:
standardized difference in means, 0.16: 95% CI, 0.29 to
0.03, P = 0.016; DBP: standardized difference in means: 0.27,
95% CI = 0.41 to 0.12, P < 0.001) (Fig. 3).

was applied for both risk factors as there was evidence of

heterogeneity among the studies (LDL-c: Q statistic = 48.77,
I2 = 77.45%, P < 0.001; HDL-c: Q statistic = 72.93, I2 = 83.55%,
P < 0.001). The standardized difference in mean change from
baseline showed no difference between groups for both HDL-c
and LDL-c (HDL-c: standardized difference in means, 0.05; 95%
CI, 0.10 to 0.21; P = 0.503; LDL-c: standardized difference in
means = 0.14; 95% CI, 0.29 to 0.02; P = 0.092) (Fig. 3).

3.6.

Sensitivity analysis was performed in which the results were

analyzed when one study was removed in turn for BMI and
HbA1c results. The direction and magnitude of the combined
estimates did not markedly change with the exclusion of
individual studies, indicating that no one study dominated
the findings (Fig. 4). Funnel plot analysis for publication bias
found the combined effect size yielded Z values of 1.96 for BMI
(P < 0.001) and 8.16 for HbA1c (P < 0.001). The Eggar's test
found funnel plot symmetry, indicating there was no significant evidence of publication bias (P = 0.148 for BMI, P = 0.572
for HbA1c) (Fig. 5).

4.
3.5.

Sensitivity analysis and publication bias

Discussion

LDL-c and HDL-c

Of the 16 studies, 12 reported change from baseline in LDL-c

[16,17,2023,25,26,2831] and 13 reported change from baseline in HDL-c [1620,2225,2831]. A random effects analysis

The effect of lifestyle interventions on risk factors associated

with cardiovascular disease in patients with type 2 diabetes is
unclear. Only a limited number of studies have investigated
this issue and they utilized a range of interventions and

Table 1 Baseline characteristics of studies included in the meta-analysis.

Type of
study

Total enrolled
patient number

Groups

Description of groups

Number of
patients

Age, y
(mean SD)

Sex, males
(n, %)

Length of
program

Ali M (2012)

RCT

48

Intervention

Pharmaceutical care package (education program of about

diabetes, its treatment and associated cardiovascular risk factors)
Seen by a pharmacist only at the beginning of the study and
then after 12 months in addition to the usual service.
Pharmacist care
Without pharmacist interventions
Supervised exercise
General advice about physical activity
Group counseling sessions over the diabetes selfmanagement regimen
Monthly contact with the study team
Education Medication Optimization group (a structured selfmanagement education program)
Standard care by their own clinician according to local guidelines
Precede Health Promotion Education (PHPE)
Conventional Health Promotion Education (CHPE)
Intensive lifestyle intervention (ILI)
Diabetes support and education (DSE)
Dietary intensive individualized dietary intervention
Usual clinical care for diabetes
Lifestyle intervention (education on lifestyle modification)
Conventional treatment
Regular, structured and personalized exercise prescription
Usual outpatient clinical care
Supervised training plus structured exercise counseling
Counseling alone as part of standard care
Additional structured health education program
Usual medical care only
Supervised by a signed case manager
Usual care from the primary care provider
Physical activity counseling intervention
Standard exercise leaflet
Systemic education program in group and individual sessions
Usual care
Intensified diet education
Usual care at local health centers

23

66.4 12.7

10, 43.5%

12 months

23

66.8 10.2

13, 56.5%

51
54
70
70
132

63.2 9.5
61.7 11.2
57 6
56 6
NA

30, 58.8%
28, 51.9%
41, 59%
40, 57%
38, 29%

6 months

133
94

NA
62.6 10.3

46, 34.8%
71, 75.5%

18 months

95
300
300
2570
2575
45
48
1017
1016
32
29
303
303
90
88
123
123
35
35
56
56
40
46

60.3 10.7
66.06 8
67.28 19
58.6 6.8
58.9 6.9
56.6 8.8
58.4 8.8
58.5 6.9
58.6 7.0
54.3 1.4
51.3 1.8
NA
NA
55.0 9.0
56.0 10.2
61 10
61 11
57.6 7.9
NA
62.0 (3580)
61.0 (4378)
NA
NA

72, 75.8%
139, 46.2%
152, 50.7%
1044, 40.7%
1038, 40.4%
17,38%
21, 44%
549, 54.0%
538, 53.0%
20,62%
18, 62%
NA
NA
44, 48.9%
34, 38.6%
121, 98%
117, 95%
35, 50%
NA
27, 48.2%
34, 60.7%
NA
NA

Control
Chan CW (2012)

RCT

120

Dobrosielski DA (2012)

RCT

140

Sevick MA (2012)

RCT

265

Intervention
Control
Intervention
Control
Intervention

Crasto W (2011)

RCT

189

Control
Intervention

Salinero-Fort MA (2011)

RCT

608

The LookAHEAD
Research Group (2010)
Coppell KJ (2010)

RCT

5145

RCT

93

Sone H (2010)

RCT

2033

Wisse W (2010)

RCT

74

Balducci S (2010)

RCT

606

Ko GT (2004)

RCT

180

Krein SL (2004)

RCT

246

Kirk A (2004)

RCT

70

Trento M (2002)

RCT

112

Uusitupa M (1993)

RCT

86

Control
Intervention
Control
Intervention
Control
Intervention
Control
Intervention
Control
Intervention
Control
Intervention
Control
Intervention
Control
Intervention
Control
Intervention
Control
Intervention
Control
Intervention
Control

9 months
26 weeks

2 years
4 years
6 months
8 years
2 years
12 months
1 year
18 months
12 months

M ET ABOL I SM CL IN I CA L A N D EX PE RI ME N TA L 6 4 ( 2 0 15 ) 33 83 4 7

Study

4 years
15 months

Abbreviations: NA, not available; RCT, randomized control trial.

Median (range: min. to max.).

341

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M ET ABOL I SM CL IN I CA L A N D E XP E RI ME N TAL 6 4 ( 2 0 15 ) 33 83 47

Fig. 2 The quality assessment for each included study was summarized in (A) risk of bias summary or (B) as percentages
across all included studies in risk of bias graph.

methodologies [1631]. Interventions included increased

physical activity, reduced caloric intake, dietary education,
and counseling and education regarding treatment adherence or disease monitoring. In general, these studies
indicated a benefit of lifestyle intervention on risk factors of
cardiovascular disease [1631]. However, not all findings
were consistent across studies. For example, Dobrosieski
et al. (2012) found no change in blood pressure with
supervised exercise [27] while, Balducci et al. (2010) found
significant improvement in both systolic and diastolic blood

pressures with supervised aerobic and resistance training

[28]. The inconsistencies among the studies may reflect the
different interventions employed.
Our meta-analysis found significant improvement with
lifestyle intervention in the cardiovascular diseaseassociated risk factors BMI, HbA1c, SBP, and DBP (all Pvalues 0.014) in patients with type 2 diabetes. HDL-c and
LDL-c levels were not significantly changed by lifestyle
intervention (P = 0.503 and P = 0.092, respectively). Sensitivity analysis indicated that the HbA1c and BMI findings were

M ET ABOL I SM CL IN I CA L A N D EX PE RI ME N TA L 6 4 ( 2 0 15 ) 33 83 4 7

343

Fig. 3 Forest plot comparing intervention and control groups for change from baseline in (top to bottom) BMI, HbA1c, SBP, DBP,
LDL-c and HDL-c. Abbreviations: CI, confidence interval; std diff, standardized difference.
not dependent on any one study and did not result from
publication bias. There are several strengths to our analysis.
For example, we focused on long-term effects of lifestyle

interventions, since only studies that were > 6 months

were included, and all included studies were randomized
controlled trials.

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M ET ABOL I SM CL IN I CA L A N D E XP E RI ME N TAL 6 4 ( 2 0 15 ) 33 83 47

Fig. 4 Sensitivity analysis of the influence of each study on the pooled estimate of (A) BMI or (B) HbA1c. The leave-one-out
approach was used. Abbreviations: CI, confidence interval; std diff, standardized difference.

Our findings are consistent with several previous metaanalyses and systematic reviews which also found that multifaceted lifestyle intervention improved several cardiovascularassociated risk factors, including BMI and HbA1c, in patients
with or at risk for type 2 diabetes [57,12,13]. One prior metaanalysis examined the effect of lifestyle intervention focused on physical activity (regular movement such as
walking) and exercise (structured activities such as cycling,
running etc.) on levels of HbA1c and BMI in patients with type
2 diabetes [5]. The meta-analysis included 17 randomized
controlled trials and found that interventions which increased
physical and exercise activity were associated with improvements in HbA1c (weighted mean difference [WMD], 0.32%, 95%
CI, 0.44% to 0.21%) and BMI (WMD, 1.05 kg/m2, 95% CI, 1.31
to 0.80) [5].
Other meta-analyses and systematic reviews found that
multi-faceted lifestyle intervention improved several cardiovascular-associated risk factors, including BMI and HbA1c, in

patients with or at risk for type 2 diabetes [6,7,10,12,13]. The

lifestyle interventions included an exercise and diet component and at least one other component such as smoking
cessation, behavior modification, and counseling. In contrast
to our study, one of the meta-analysis did not find intervention significantly improves systolic or diastolic blood pressure
[7]. It also found, using sensitivity analysis, that there was
improvement in HDL (mean difference, 0.04; 95% CI, 0.030.05)
and HbA1c (mean difference, 0.71; 95% CI, 1.31 to 00.12)
only for interventions that included pharmacotherapy [7].
In addition, these improvements did not continue past the
interventional phase [7]. We did not evaluate the relationship
of lifestyle intervention with pharmacotherapy or treatment
duration in our analysis.
Another meta-analysis specifically assessed whether resistance exercise is comparable to aerobic exercise in regard to
glycemic control, blood lipids, blood pressure, anthropometric
measures, health status, and adverse events [10]. Twelve

M ET ABOL I SM CL IN I CA L A N D EX PE RI ME N TA L 6 4 ( 2 0 15 ) 33 83 4 7

Fig. 5 Funnel plots for publication bias (A) BMI and

(B) HbA1c. Abbreviations: std diff, standardized difference.

randomized controlled studies that included 626 patients with

type 2 diabetes ( 18 years of age) were included in the metaanalysis. The analysis found that aerobic exercise was
associated with a greater reduction in HbA1c compared with
resistance exercise (18% difference [1.97 mmol/mol; 95% CI,
0.010.36]). However with sensitivity analysis, the difference
was non-significant (P = 0.14). Significant differences from
baseline in favor of aerobic exercise were also observed for
BMI, peak oxygen consumption, and maximum heart rate.
Importantly, the difference between exercise regimens was
not clinically important, and the authors conclude that
physical activity in general may be more important than the
choice of a specific exercise [10].
One systematic review analyzed a combination of 3 groups
of patients: those at risk for type 2 diabetes, those at risk for
cardiovascular disease, and those with type 2 diabetes [6].
They found that lifestyle intervention did not improve SBP,
DBP, or HDL. However, the fact their study evaluated a
heterogeneous population of patients makes it difficult to
compare their finding with ours. Similar to our findings, the
analysis did not find lifestyle intervention affected LDL levels.
Two other systematic reviews evaluated whether behavioral
changes, such as exercise training/physical activity and/or
nutritional intervention, impacted the incidence of type 2
diabetes in subjects at risk for the disease [12,13]. They found
that although there was wide variability in efficacy, all the
included studies indicated that behavioral changes that
included modification of diet and exercise reduced the
incidence of type 2 diabetes compared with controls, with a
relative risk reduction of 39%75%. The systematic review also
found a benefit in weight change and a reduction in BMI. In

345

addition, both reviews indicated that adopting a long-term

approach in changing behavior with several interventional
components was most successful.
A literature review identified over 100 studies that assessed
the role of physical activity on cardiovascular disease in
subjects with diabetes [11]. The authors conclude that overall
the literature suggests physical activity reduces the risk of
cardiovascular disease in people with diabetes. However, they
comment that a number of drug trials do not support the idea
that reduction of blood glucose concentration reduces cardiovascular disease. Why exercise reduces the risk of cardiovascular disease in patients with diabetes is unclear.
There are several limitations to our analysis that should be
considered when interpreting the findings. The included
studies used diverse forms of interventions and there was
little detail regarding the specifics of intervention methodology. Due to the lack of experimental detail in many published
studies, it is possible that other studies may have been missed
due poor descriptions of lifestyle interventions. We grouped
all the types of interventions for our analysis; hence, it is not
possible to evaluate or compare the efficacy of each type of
intervention with improving markers of cardiovascular disease. All included studies had a high risk for bias in regard to
blinding of the participants and personnel that may have
affected outcomes. The different included studies had a wide
range of variability in age, sex, and duration of follow up
which could have confounded our findings. Ideally, we would
have used subgroup analysis to address this problem.
However, due to the limitation of extracting sufficient data
for each confounder, we were unable to perform this type of
analysis. Another possible confounding factor is the potential
difference between groups in drug prescriptions. Drug prescription information was only reported in 5 of the studies
[21,2325,31] and the data in these studies were not sufficient
to allow us to perform multivariate analysis to adjust for
differences in drug prescriptions. Although our funnel plot
analysis indicated there was no publication bias, this conclusion is limited owing to the large degree of clinical heterogeneity across the included studies. We did not assess the effect
of lifestyle intervention on death or adverse events due to
cardiovascular disease; therefore, it is not clear how the
changes we see in cardiovascular disease-associated risk
factors reflect these clinical outcomes.

5.

Conclusion

In summary, our meta-analysis found that lifestyle intervention which included change in diet, exercise, and education
showed significant benefit in a number of risk factors which
are known to be associated with cardiovascular disease in
patients with type 2 diabetes.
Supplementary data to this article can be found online at
http://dx.doi.org/10.1016/j.metabol.2014.10.018.

Author contributions
Liang Chen: guarantor of integrity of the entire study; Jian-Hao
Pei: study concepts; Jian Kuang: study design, statistical

346

M ET ABOL I SM CL IN I CA L A N D E XP E RI ME N TAL 6 4 ( 2 0 15 ) 33 83 47

analysis; Hong-Mei Chen: data analysis; Zhong Chen:

manuscript preparation; Zhong-Wen Li: manuscript editing;
Hua-Zhang Yang: manuscript review.

Acknowledgments
None.

Conflict of interest
None.

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